Back to Search
Start Over
Isolation of pathogenic monoclonal anti-desmoglein 1 human antibodies by phage display of pemphigus foliaceus autoantibodies.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2008 Apr; Vol. 128 (4), pp. 939-48. Date of Electronic Publication: 2007 Nov 15. - Publication Year :
- 2008
-
Abstract
- Pemphigus foliaceus (PF) is a blistering disease caused by autoantibodies to desmoglein 1 (Dsg1) that cause loss of epidermal cell adhesion. To better understand PF pathophysiology, we used phage display to isolate anti-Dsg1 mAbs as single-chain variable fragments (scFvs) from a PF patient. Initial panning of the library isolated only non-pathogenic scFvs. We then used these scFvs to block non-pathogenic epitopes and were able to isolate two unique scFvs, each of which caused typical PF blisters in mice or human epidermis models, showing that a single mAb can disrupt Dsg1 function to cause disease. Both pathogenic scFvs bound conformational epitopes in the N terminus of Dsg1. Other PF sera showed a major antibody response against the same or nearby epitopes defined by these pathogenic scFvs. Finally, we showed restriction of the heavy-chain gene usage of all anti-Dsg1 clones to only five genes, which determined their immunological properties despite promiscuous light-chain gene usage. These mAbs will be useful for studying Dsg1 function and mechanisms of blister formation in PF and for developing targeted therapies and tools to monitor disease activity.
- Subjects :
- Aged
Animals
Antibodies, Monoclonal genetics
Antibodies, Monoclonal immunology
Autoantibodies genetics
Autoantibodies immunology
Desmoglein 1 analysis
Desmoglein 1 antagonists & inhibitors
Epitope Mapping
Epitopes immunology
Female
Fluorescent Antibody Technique, Indirect
Humans
Immunoglobulin Heavy Chains genetics
Immunoglobulin Heavy Chains immunology
Immunoglobulin Heavy Chains isolation & purification
Immunoglobulin Variable Region immunology
Immunoglobulin Variable Region isolation & purification
Mice
Skin immunology
Antibodies, Monoclonal isolation & purification
Autoantibodies isolation & purification
Desmoglein 1 immunology
Pemphigus immunology
Peptide Library
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 128
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 18007588
- Full Text :
- https://doi.org/10.1038/sj.jid.5701132